The primary objective of this program is the preparation and initial biological evaluation of analogs of the antitumor antibiotic adriamycin with a view toward improving the therapeutic efficacy, extending the antitumor spectrum and/or reducing the toxicity of the parent anthracycline. Based upon an earlier lead developed in this laboratory, namely, the greater antitumor effect and lesser toxicity of N-trifluoroacetyladriamycin-14-valerate (AD 32) compared to adriamycin, a number of adriamycin analogs have been synthesized both as candidate anticancer agents and to explore the structure-activity relationships. Some of these products were used in conjunction with preliminary DNA-binding studies which showed that AD 32 did not bind with calf thymus DNA and that the lack of binding was due to the trifluoroacetyl substitution and not to the valeric ester (S.K. Sengupta, R. Seshadri, E.J. Modest, M. Israel, Proc. Amer. Assoc. Cancer Research, 17, (1976), in press). Other functional derivatives of the 14-position methyl group of daunorubicin have included 14-aza- and 14-thioadriamycin analogs, with and without the trifluoroacetyl substitution on the glycosidic amine. The daunorubicin and adriamycin analogs wherein the daunosamine moiety has been replaced by D-glucosamine and N-trifluoroacetyl-D-glucosamine have been prepared and are currently undergoing in vivo antitumor evaluation in mice bearing the L1210 leukemia. Other glycosidic modifications are in progress.